Sodium–glucose cotransporter inhibitors as add‐on therapy in addition to insulin for type 1 diabetes mellitus: A meta‐analysis of randomized controlled trials

Abstract

Aims/Introduction: Several clinical trials reported the effects of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes patients. This meta-analysis aimed to assess the efficacy and safety of SGLT inhibitors in type 1 diabetes patients. Materials and Methods: Relevant studies were identified in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases through 1 April 2020. Differences were expressed as the 95% confidence interval (CI) or weighted mean difference (WMD) for continuous outcomes, and risk ratio (RR) for discontinuous outcomes. Results: A total of 13 RCTs with 7,962 cases were included. SGLT inhibitors reduced the fasting plasma glucose level (WMD-1.320 mmol/L, 95% CI-1.609 to-1.031, P < 0.001), glycated hemoglobin level (WMD-0.386%, 95% CI-0.431 to-0.342, P < 0.001) and daily total insulin dose (WMD-5.403, 95% CI-7.218 to-3.859, P < 0.001). However, higher risks of diabetic ketoacidosis (RR 5.042, 95% CI 3.160-8.046, P < 0.001), urinary tract infections (RR 1.259, 95% CI 1.034-1.533, P = 0.022) and genital infections (RR 2.995, 95% CI 1.953-4.594, P < 0.001) were associated with SGLT inhibitors, but SGLT inhibitors did not increase the hypoglycemia risk (RR 0.980, 95% CI 0.840-1.144, P = 0.799). In subgroup analysis, with a significant reduction of fasting plasma glucose, glycated hemoglobin and daily insulin doses, SGLT1/2 inhibitor did not increase genitourinary tract infections compared with a placebo. Conclusions: SGLT2 and SGLT1/2 inhibitors can improve glycemic control in patients with type 1 diabetes.

Strategically Playing with Fire: SGLT Inhibitors as Possible Adjunct to Closed-Loop Insulin Therapy

“…The summated reductions are in HbA1c by 0.39%, weight by 3.47%, mean glucose by 1.07 mmol/L, TDD by 10.4%, and systolic blood pressure 3.37 mmHg. 70-73 CGM data revealed improvements in TIR without increased hypoglycemia. 59,62,64,66,74 Unfortunately, the relative risks of ketoacidosis in those treated with SGLTi compared to placebo were 3-5.…”

“…59,62,64,66,74 Unfortunately, the relative risks of ketoacidosis in those treated with SGLTi compared to placebo were 3-5. 70-73…”

“…The trials demonstrated in Table 1 revealed decrease in mean fasting glucose, mean glucose throughout the day, and glycemic variability with SGLTi use. 70,72,73,87 While improved overnight glucose control is novel in SGLTi use with routine insulin therapy, HCL has already shown superior nocturnal glycemia. 18,20,88 Given daytime hyperglycemia is the main obstacle, SGLTi-induced reductions in glucose variability may blunt these rises.…”

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium–glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020)

“…In a meta‐analysis of 13 RCTs including 7962 participants, there was higher risk of DKA (RR 5.04), UTI (RR 1.2) and genital infections (RR 2.99) but not hypoglycaemia 44 …”

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose co-transporter inhibitors with insulin for treatment of type 1 diabetes (updated October 2020)

“…43 In a meta-analysis of 13 RCTs including 7,962 participants, there was a higher risk of DKA (RR 5.04), urinary tract infections (RR 1.2) and genital infections (RR 2.99) but not hypoglycaemia. 44 Sotagliflozin meta-analysis of seven RCTs including nearly 3,600 participants showed a higher rate of DKA (RD 0.03) and genital mycotic infections (RD 0.06) but no increase in urinary tract infections compared with placebo. 39 People with type 1 diabetes develop DKA in the absence of insulin.…”